EP0801948B1 - Ophtalmische Zusammensetzung mit verlängerter Verweilzeit am Auge - Google Patents
Ophtalmische Zusammensetzung mit verlängerter Verweilzeit am Auge Download PDFInfo
- Publication number
- EP0801948B1 EP0801948B1 EP97103736A EP97103736A EP0801948B1 EP 0801948 B1 EP0801948 B1 EP 0801948B1 EP 97103736 A EP97103736 A EP 97103736A EP 97103736 A EP97103736 A EP 97103736A EP 0801948 B1 EP0801948 B1 EP 0801948B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- eye
- weight percent
- ophthalmic
- dimethyl ammonium
- preservative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 230000002035 prolonged effect Effects 0.000 title claims description 5
- 239000000203 mixture Substances 0.000 title description 26
- 239000003755 preservative agent Substances 0.000 claims abstract description 27
- 230000007794 irritation Effects 0.000 claims abstract description 11
- 230000000451 tissue damage Effects 0.000 claims abstract description 9
- 231100000827 tissue damage Toxicity 0.000 claims abstract description 9
- CYDRXTMLKJDRQH-UHFFFAOYSA-N benzododecinium Chemical class CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 CYDRXTMLKJDRQH-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 239000013543 active substance Substances 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 22
- 230000002335 preservative effect Effects 0.000 claims description 11
- JBIROUFYLSSYDX-UHFFFAOYSA-M benzododecinium chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 JBIROUFYLSSYDX-UHFFFAOYSA-M 0.000 claims description 9
- 239000000607 artificial tear Substances 0.000 claims description 5
- 239000003889 eye drop Substances 0.000 claims description 5
- 229940012356 eye drops Drugs 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 3
- 239000000600 sorbitol Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 229940096529 carboxypolymethylene Drugs 0.000 claims 1
- 239000006196 drop Substances 0.000 claims 1
- 150000004678 hydrides Chemical class 0.000 claims 1
- 239000012530 fluid Substances 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 239000002674 ointment Substances 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 22
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 6
- 229960004906 thiomersal Drugs 0.000 description 6
- 229920002125 Sokalan® Polymers 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 206010015946 Eye irritation Diseases 0.000 description 3
- 210000004087 cornea Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 231100000013 eye irritation Toxicity 0.000 description 3
- 230000036512 infertility Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 229920005615 natural polymer Polymers 0.000 description 3
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229960001716 benzalkonium Drugs 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229940057917 medium chain triglycerides Drugs 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019155 vitamin A Nutrition 0.000 description 2
- 239000011719 vitamin A Substances 0.000 description 2
- 229940045997 vitamin a Drugs 0.000 description 2
- 241000700198 Cavia Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 229920013820 alkyl cellulose Polymers 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 231100000040 eye damage Toxicity 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 238000005189 flocculation Methods 0.000 description 1
- 230000016615 flocculation Effects 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 231100001032 irritation of the eye Toxicity 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 229940100655 ophthalmic gel Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Definitions
- the invention relates the use of a benzyllauryldimethylammonium salt for the preparation of ophthalmic compositions for repeated use are intended for longer periods and / or for a longer period of time on the eye after each Application are formulated to avoid those caused by benzalkonium chloride Irritation and / or tissue damage to the eye.
- Ophthalmic compositions like other pharmaceuticals Preparations, too, from various types of microorganisms be contaminated. It must be avoided that such microorganisms when using the ophthalmic composition in can get into the eye and onto the mucous membranes of the eyes. Ophthalmic Preparations therefore have high sterility requirements satisfy. For this reason, the manufacture of such Preparations are always carried out under sterile conditions.
- these preservatives are added. On the one hand, these must have a sufficient germicidal effect to ensure the permanent sterility of the preparation, on the other hand, they are not allowed to cause irritation or tissue damage themselves of the eye, which is often already damaged.
- ophthalmic compositions that after a single application one (in comparison with slightly through Tear fluid washable preparations, such as usual aqueous Drip solutions) prolonged dwell time on or in the eye demonstrate.
- Such preparations are in terms of their consistency increased viscosity set.
- An example are by adding water-soluble polymers gel-like thickened aqueous preparations, especially so-called drip gels.
- Another example are the known ointments, mostly in the form of spreadable emulsions.
- Preservatives for such purposes are e.g. Thiomersal, Centrimid, and the like. Substances in use.
- Another commonly suggested preservative for ophthalmic preparations is benzalkonium chloride.
- Benzalkonium chloride is the international free name for N-alkyl-N-benzyl-N, N-dimethylammonium chloride, with alkyl residues between C 8 H 17 and C 18 H 37 .
- Benzalkonium chloride is usually obtained from natural fats or oils and, depending on the raw materials used, is a mixture of changing compositions of the quaternary compounds described above.
- benzalkonium always means such a mixture with different alkyl radicals, the number of carbon atoms in the alkyl radical varying from C 8 to C 18 .
- French patent application FR-2 678 832 describes ophthalmic compositions containing various active ingredients and polyacrylic acid as a thickener to achieve a lasting effect on the eye.
- FR-2 678 832 makes no statements about the compatibility of the preservatives used, especially not for long and repeated use.
- ophthalmic preparations are in Various forms of application known, which by adding an osmotically compatible antimicrobial substance can be made more tolerable to the eye.
- the described Usable preservatives also include benzalkonium chloride, which long-term or repeated use is irritating to the eyes.
- Benzyllauryldimethylammoniumchlorid and its irritation-avoiding effect is in the FR-2 679 773 not mentioned.
- Benzalkonium chloride has excellent antiseptic properties even in ophthalmic Preparations, in particular in aqueous ophthalmic preparations.
- points Benzalkonium chloride as has been shown since the publication of the aforementioned patents, poor tolerance, which can lead to irritation and even lesions of the eye.
- B. Lopez et al. (Current Eye Research, 1991, 10 (7.645 to 656) report the damaging Effect of preservatives in artificial tears on the cornea in rabbits. The effect of tear fluids containing 0.01% benzalkonium chloride, 0.001% polyquat or 0.004% thiomersal was conserved Comparison group, in which artificial tear fluid without preservatives used has been.
- the measure of damage to the cornea was the increase in absorption for Carboxyfluorescein chosen. Artificial tears containing polyquat or thiomersal caused an up to fourfold increase in admission. Artificial tears, the benzalkonium chloride contained an approximately 10 to 100-fold increase in admission.
- Electron microscopic control examinations showed that the increase in Absorption capacity for carboxyfluorescein with increased cell damage in the cornea went along. As a result, the use of benzalkonium salts for ophthalmics strongly discouraged.
- JP-A 1246227 describes a method for avoiding incompatibilities in liquid aqueous ophthalmic compositions, in particular eye drops which contain benzalkonium chloride.
- a large number of medicinal active substances in the dosage form as an aqueous solution show incompatibility with benzalkonium chloride, which leads to the formation and flocculation of soluble compounds. It is therefore not possible to use benzalkonium chloride as a preservative in such aqueous compositions.
- almost pure benzyllauryldimethylammonium chloride i.e.
- the object of the present invention is an ophthalmic composition to provide the type mentioned at the outset good tolerance to the eye, even with long-term exposure, and overcomes the disadvantages of the prior art, without the beneficial effects of the benzalkonium salts to give up as a preservative.
- the invention therefore makes it possible in particular to use such ophthalmic Preserve compositions compared to one extended dwell time on the eye with eye drops or the like should have.
- dripping gels, ointments and the like can be created after a single application act on the eye for a long time because they are slow through the eye Tear fluid can be washed out using the preservative has all the advantages of the known benzalkonium chloride, but without causing eye irritation or even eye damage Effect.
- compositions around those which, as carriers, have an aqueous have drippable gel base. You will be in a known manner a viscosity-increasing synthetic or natural polymer use in aqueous solution or aqueous dispersion.
- gel formers are particularly suitable for this Carboxyvinyl polymers, especially carboxypolymethylenes, which are commercially available under the "Carbopol” brand. Alternatively, they can be obtained commercially under the "EMA” brand Use ethylene-maleic anhydride copolymers.
- the various natural polymers are particularly suitable again cellulose derivatives already known for ophthalmic gels, especially alkyl celluloses, hydroxy celluloses, Hydroxyalkyl celluloses, etc.
- additional or alternatively use natural rubbers, such as Guar gum, xanthan gum, etc.
- Further examples of the invention natural polymers which can advantageously be used are dextran and its derivatives.
- composition as a basically single-phase aqueous liquid to formulate in which the other components are dissolved or as dispersed particles occur.
- the composition can be used as two-phase liquid are built up with an aqueous and a hydrophobic phase.
- the preparation determined Active ingredients such as those containing vitamin A
- a continuous aqueous phase with droplets emulsified therein the hydrophobic phase are suitable as a hydrophobic phase
- Use medium-chain triglycerides as the hydrophobic phase are particularly advantageous.
- the concentration of the benzyllauryldimethylammonium salt corresponds the usual concentrations as for benzalkonium chloride can be scheduled.
- the benzyllauryldimethylammonium salt is preferably simply the chloride.
- the advantage of the invention can also be for use such ophthalmic compositions, although none viscosity-increasing (and thus delaying washing out) Ingredients included, but repeated over long periods must be applied and thus also to a permanently increased Keep a preservative level in the eye.
- Such preparations too can, if contain harmful preservatives cause irritation or even tissue damage and therefore, the preparation according to the invention can also be used for such preparations Take advantage by using the benzyllauryldimethylammonium salt instead of these preservatives used as a preservative become.
- Examples include not only eye drops, but also artificial ones Tear fluid, such as that reported by Lopez et al Attempt.
- Ophthalmic composition with 0.01% benzyllauryldimethylammonium chloride.
- Neck size 2 kg ingredients Quantity in grams Carbopol 980 NF 4.00 Benzyllauryldimethylammonium chloride 0.2000 Sorbitol 80.00 NaOH, firm 1.57 water (Rest up to batch size)
- Ophthalmic composition with 0.005% benzyllauryldimethylammonium chloride.
- Neck size 2 kg ingredients Quantity in grams Carbopol 980 NF 4.00 Benzyllauryldimethylammonium chloride 0.1000 Sorbitol 80.00 NaOH, firm 1.57 water (Rest up to batch size)
- Long-term tests on guinea pigs (Charles River) were carried out with the compositions according to Examples 1 and 2.
- comparative tests were carried out with a corresponding control group, in which the same compositions were used in all respects, but differing in terms of the preservative.
- the test duration was 5 weeks.
- the ophthalmic compositions according to the Examples 1 and 2 according to the invention did not end in any rabbit the duration of the experiment to a noticeable irritation of the eye. No tissue damage was observed either.
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI9730178T SI0801948T1 (en) | 1996-04-15 | 1997-03-06 | Ophthalmic composition having prolonged residence time in the eye |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19614823 | 1996-04-15 | ||
| DE19614823A DE19614823A1 (de) | 1996-04-15 | 1996-04-15 | Ophthalmische Zusammensetzung mit verlängerter Verweilzeit am Auge |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0801948A1 EP0801948A1 (de) | 1997-10-22 |
| EP0801948B1 true EP0801948B1 (de) | 2001-06-06 |
Family
ID=7791310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP97103736A Expired - Lifetime EP0801948B1 (de) | 1996-04-15 | 1997-03-06 | Ophtalmische Zusammensetzung mit verlängerter Verweilzeit am Auge |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US6599944B1 (pl) |
| EP (1) | EP0801948B1 (pl) |
| JP (1) | JP4582822B2 (pl) |
| CN (1) | CN1215988A (pl) |
| AT (1) | ATE201820T1 (pl) |
| AU (1) | AU714093B2 (pl) |
| BR (1) | BR9708669A (pl) |
| CA (1) | CA2251982C (pl) |
| DE (2) | DE19614823A1 (pl) |
| DK (1) | DK0801948T3 (pl) |
| ES (1) | ES2159783T3 (pl) |
| GR (1) | GR3036498T3 (pl) |
| PL (1) | PL187339B1 (pl) |
| PT (1) | PT801948E (pl) |
| SI (1) | SI0801948T1 (pl) |
| WO (1) | WO1997038674A1 (pl) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19614823A1 (de) | 1996-04-15 | 1997-10-16 | Mann Gerhard Chem Pharm Fab | Ophthalmische Zusammensetzung mit verlängerter Verweilzeit am Auge |
| DE19744113A1 (de) * | 1997-10-06 | 1999-04-15 | Mann Gerhard Chem Pharm Fab | Dexamethason-Gel |
| IN185228B (pl) * | 1999-02-03 | 2000-12-09 | Bakulesh Mafatlal Dr Khamar | |
| DE19918324A1 (de) * | 1999-04-22 | 2000-10-26 | Mann Gerhard Chem Pharm Fab | Pharmazeutische Zusammensetzung wirksam gegen durch Bakterien, Viren, Pilze, Hefen und Protozoen verursachte Krankheitszustände |
| DE19938668B4 (de) * | 1999-08-14 | 2006-01-26 | Bausch & Lomb Inc. | Tränenersatzmittel |
| DE10132876A1 (de) * | 2001-07-06 | 2003-01-30 | Medproject Pharma Entwicklungs | Zweiphasige, tropfbare Hydrogele zur Anwendung am Auge |
| US8545487B2 (en) * | 2007-12-05 | 2013-10-01 | Avedro Inc. | Eye therapy system |
| US8366689B2 (en) * | 2008-09-30 | 2013-02-05 | Avedro, Inc. | Method for making structural changes in corneal fibrils |
| US8574277B2 (en) | 2009-10-21 | 2013-11-05 | Avedro Inc. | Eye therapy |
| WO2011116306A2 (en) | 2010-03-19 | 2011-09-22 | Avedro, Inc. | Systems and methods for applying and monitoring eye therapy |
| US9044308B2 (en) | 2011-05-24 | 2015-06-02 | Avedro, Inc. | Systems and methods for reshaping an eye feature |
| EP2713849B1 (en) | 2011-06-02 | 2017-02-15 | Avedro, Inc. | Systems for monitoring time based photo active agent delivery or photo active marker presence |
| CN102416011A (zh) * | 2011-10-10 | 2012-04-18 | 艾硕特生物科技（昆明）有限公司 | 一种广谱、高效的抗菌洗液 |
| EP3808339B1 (en) | 2012-05-03 | 2025-11-12 | Alcon Inc. | Pharmaceutical nanoparticles showing improved mucosal transport |
| US11596599B2 (en) | 2012-05-03 | 2023-03-07 | The Johns Hopkins University | Compositions and methods for ophthalmic and/or other applications |
| US9827191B2 (en) | 2012-05-03 | 2017-11-28 | The Johns Hopkins University | Compositions and methods for ophthalmic and/or other applications |
| WO2013166385A1 (en) | 2012-05-03 | 2013-11-07 | Kala Pharmaceuticals, Inc. | Pharmaceutical nanoparticles showing improved mucosal transport |
| EP2872081B2 (en) | 2012-07-16 | 2025-07-16 | Avedro, Inc. | Systems for corneal cross-linking with pulsed light |
| US9498122B2 (en) | 2013-06-18 | 2016-11-22 | Avedro, Inc. | Systems and methods for determining biomechanical properties of the eye for applying treatment |
| US9498114B2 (en) | 2013-06-18 | 2016-11-22 | Avedro, Inc. | Systems and methods for determining biomechanical properties of the eye for applying treatment |
| US9308165B2 (en) * | 2013-08-22 | 2016-04-12 | Therapeutic Vision, Inc. | Composition for treating ocular effects of diabetes |
| EP3212140B1 (en) | 2014-10-27 | 2021-12-01 | Avedro, Inc. | Systems for cross-linking treatments of an eye |
| WO2016077747A1 (en) | 2014-11-13 | 2016-05-19 | Avedro, Inc. | Multipass virtually imaged phased array etalon |
| US10258809B2 (en) | 2015-04-24 | 2019-04-16 | Avedro, Inc. | Systems and methods for photoactivating a photosensitizer applied to an eye |
| WO2016191342A1 (en) | 2015-05-22 | 2016-12-01 | Avedro, Inc. | Systems and methods for monitoring cross-linking activity for corneal treatments |
| CN116832158A (zh) | 2015-07-21 | 2023-10-03 | 艾维德洛公司 | 用光敏剂治疗眼睛的系统和方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1399834A (en) * | 1971-05-12 | 1975-07-02 | Fisons Ltd | Pharmaceutical compositions |
| US4053628A (en) * | 1971-05-12 | 1977-10-11 | Fisons Limited | Composition |
| AU499860B2 (en) * | 1975-04-24 | 1979-05-03 | Honda Giken Kogyo Kabushiki Kaisha | Deflector plate to equalise fuel distribution in induction gas flow |
| JPS5313588A (en) * | 1976-07-23 | 1978-02-07 | Alcon Lab Inc | Ophthalmic solution |
| GB2013084B (en) * | 1978-01-25 | 1982-07-28 | Alcon Lab Inc | Ophthalmic drug dosage |
| US4271143A (en) * | 1978-01-25 | 1981-06-02 | Alcon Laboratories, Inc. | Sustained release ophthalmic drug dosage |
| DE3415663A1 (de) * | 1984-04-27 | 1985-10-31 | Sandoz-Patent-GmbH, 7850 Lörrach | Eine neue ophthalmologische verabreichungsform |
| US4738851A (en) * | 1985-09-27 | 1988-04-19 | University Of Iowa Research Foundation, Inc. | Controlled release ophthalmic gel formulation |
| US5032392A (en) * | 1986-09-04 | 1991-07-16 | Vision Pharmaceuticals | Aqueous ophthalmic solutions for the treatment of dryness and/or irritation of human or animal eyes |
| FR2665635A1 (fr) * | 1990-08-10 | 1992-02-14 | Merck Sharp & Dohme | Composition pharmaceutique fluide a base d'un complexe metallique et son procede de preparation. |
| FR2678832B1 (fr) | 1991-07-10 | 1995-03-17 | Europhta Sa Laboratoire | Nouvelles compositions ophtalmiques a resorption amelioree et leurs procedes de preparation. |
| FR2679773A1 (fr) | 1991-07-30 | 1993-02-05 | Merck Sharp & Dohme | Preparation ophtalmique contenant un agent osmotique acceptable antimicrobien. |
| WO1994010976A1 (en) * | 1992-11-16 | 1994-05-26 | Ciba Vision Ag, Hettlingen | Polyvinyl alcohol/borate ophthalmic drug delivery system |
| WO1994015597A1 (en) * | 1993-01-11 | 1994-07-21 | Allergan, Inc. | Ophthalmic compositions comprising benzyllauryldimethylammonium chloride |
| DE19614823A1 (de) | 1996-04-15 | 1997-10-16 | Mann Gerhard Chem Pharm Fab | Ophthalmische Zusammensetzung mit verlängerter Verweilzeit am Auge |
-
1996
- 1996-04-15 DE DE19614823A patent/DE19614823A1/de not_active Withdrawn
-
1997
- 1997-03-06 AT AT97103736T patent/ATE201820T1/de active
- 1997-03-06 DE DE59703711T patent/DE59703711D1/de not_active Expired - Lifetime
- 1997-03-06 CN CN97193787A patent/CN1215988A/zh active Pending
- 1997-03-06 PT PT97103736T patent/PT801948E/pt unknown
- 1997-03-06 JP JP53667697A patent/JP4582822B2/ja not_active Expired - Lifetime
- 1997-03-06 DK DK97103736T patent/DK0801948T3/da active
- 1997-03-06 WO PCT/EP1997/001138 patent/WO1997038674A1/de not_active Ceased
- 1997-03-06 EP EP97103736A patent/EP0801948B1/de not_active Expired - Lifetime
- 1997-03-06 ES ES97103736T patent/ES2159783T3/es not_active Expired - Lifetime
- 1997-03-06 BR BR9708669A patent/BR9708669A/pt not_active IP Right Cessation
- 1997-03-06 PL PL97328656A patent/PL187339B1/pl unknown
- 1997-03-06 US US09/171,344 patent/US6599944B1/en not_active Expired - Lifetime
- 1997-03-06 CA CA002251982A patent/CA2251982C/en not_active Expired - Lifetime
- 1997-03-06 SI SI9730178T patent/SI0801948T1/xx unknown
- 1997-03-06 AU AU20246/97A patent/AU714093B2/en not_active Ceased
-
2001
- 2001-08-31 GR GR20010401358T patent/GR3036498T3/el unknown
-
2003
- 2003-07-23 US US10/625,634 patent/US20040071778A1/en not_active Abandoned
Non-Patent Citations (2)
| Title |
|---|
| FALBE J et al., 'Römpp Chemie Lexikon', Seite 1511, 9. Auflage 1990, Georg Thieme Verlag, Stuttgart * |
| LIST, "Arzneiformenlehre", Seite 442, 4. Auflage, 1985, Wissenschaftliche Verlagsgesellschaft, Stuttgart * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0801948A1 (de) | 1997-10-22 |
| ATE201820T1 (de) | 2001-06-15 |
| US6599944B1 (en) | 2003-07-29 |
| DK0801948T3 (da) | 2001-09-10 |
| DE59703711D1 (de) | 2001-07-12 |
| WO1997038674A1 (de) | 1997-10-23 |
| CA2251982A1 (en) | 1997-10-23 |
| DE19614823A1 (de) | 1997-10-16 |
| CA2251982C (en) | 2008-01-29 |
| PL187339B1 (pl) | 2004-06-30 |
| CN1215988A (zh) | 1999-05-05 |
| PL328656A1 (en) | 1999-02-15 |
| GR3036498T3 (en) | 2001-11-30 |
| JP2000508646A (ja) | 2000-07-11 |
| ES2159783T3 (es) | 2001-10-16 |
| AU714093B2 (en) | 1999-12-16 |
| AU2024697A (en) | 1997-11-07 |
| SI0801948T1 (en) | 2001-10-31 |
| BR9708669A (pt) | 1999-08-03 |
| PT801948E (pt) | 2001-10-31 |
| US20040071778A1 (en) | 2004-04-15 |
| JP4582822B2 (ja) | 2010-11-17 |
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